Inclusion Criteria:
1. Is capable of understanding and complying with protocol requirements.
2. The participants or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. Has a primary diagnosis of schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition \[DSM-5\], 295.90) confirmed by clinical interview (Structured Clinical Interview for DSM-5 Clinical Trial Version \[SCID-5-CT\]). The participant's initial diagnosis must be greater than or equal to (\>=) 1 year from screening.
4. Is a man or woman age 18 to 65, inclusive, at Screening.
5. Male participant who is nonsterilized and sexually active with a female partner of child bearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.
6. Female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose.
7. The participant's psychotic symptoms were exacerbated within 2 months (60 days) prior to Screening (example, aggravated delusion).
8. Has a score of 5 (moderate severe) or higher in 3 or more items of the following Positive and Negative Symptom Scale (PANSS) items at Screening and Day 1: delusions (P1), conceptual disorganization (P2), hallucinations (P3), suspiciousness (P6), and unusual thought content (G9).
9. Has a PANSS total score of 80 or higher at Screening and Day 1.
10. Has a Clinical Global Impression Scale- Severity of Illness Scale (CGI-S) of 4 or greater at Screening and Day 1.
11. Is able and agrees to remain off prior antipsychotic medication and all excluded medications as outlined in the protocol for the duration of the study.
12. Has an identified, reliable caregiver. A caregiver is defined as a family member, informant or friend who is able and willing to assist and support the administration of study drug, adherence to protocol requirements and to the study schedule.
13. Has a body mass index (BMI) score between 18.0 and 35.0 kilogram per square meter (kg/m\^2), inclusive, at Screening.
Exclusion Criteria:
1. Has received any investigational compound within 30 days prior to Screening, or within 5 half-lives prior to screening, whichever is longer.
2. Has received TAK-063 in a previous clinical study or as a therapeutic agent or has previously or is currently participating in this study or have participated in 2 or more clinical studies within 12 months prior to Screening.
3. Has a decrease in the PANSS Total Score by 20 percent (%) or more at Baseline (Day 1) compared with that at Screening \[(PANSS Total Score at Screening- PANSS total score at Baseline)/(PANSS Total Score at Screening- 30)\]\*100 \>=20%\].
4. Is an immediate family member, study site employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, and sibling) or may consent under duress.
5. Has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality (other than the disease being studied), which may impact the ability of the participant to participate or potentially confound the study results.
6. Has a history of severe head injury/traumatic brain injury, myocardial infarction or stroke.
7. Has a known hypersensitivity to any component of the formulation of TAK-063 or the practice pills (i.e., small colored candies) during the AiCure device training.
8. Has a positive urine drug result (illicit, illegal or without valid prescription or medical need) at Screening.
9. Has a moderate or severe substance use disorder (meeting more than 5 diagnostic criteria of DSM-5 either currently or within the last 6 months) for alcohol or other substances of abuse except nicotine or caffeine.
10. Has taken any excluded medication, supplements, or food products or has had insufficient washout of medications, supplements, or food products as listed in the Excluded /Allowed Medications, Procedures, and Treatments table or is unable or unwilling to discontinue medications as required by the protocol.
11. If female, the participant is pregnant or lactating or intending to become pregnant (a positive pregnancy test at Screening or Day 1), or intending to donate ova, before or during the course of the study or within 12 weeks after last dose.
12. If male, the participant intends to donate sperm during the course of this study or for 12 weeks after last dose.
13. Has a psychiatric disorder other than schizophrenia as their primary diagnosis.
14. Has a history of or known personality disorder or other psychiatric disorder that, in the opinion of the investigator, would interfere with participation in the study.
15. Has a history of neuroleptic malignant syndrome, water intoxication, or paralytic ileus or other conditions that may interfere with absorption of study medication.
16. Is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property or participants who within the past year prior to Screening have attempted suicide or have positive answers on item 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening or Day 1.
17. Has Parkinson disease, tardive dyskinesia, or other chronic movement disorder that may interfere with the interpretation of study results.
18. Has any existing or previous history of cancer that has been in remission for less than 5 years prior to Screening. (This criterion does not include those participants with basal cell, stage I squamous cell skin cancer or in situ cervical cancer).
19. Has newly diagnosed diabetes or requiring insulin for their treatment; diabetic participants that have had changes to their diabetic treatment regimen within 30 days prior to screening or diabetic participants that have had hospitalizations for their diabetes and/or diabetes related conditions in the past year prior to screening.
20. Has long QT syndrome or under the treatment with Class 1A (example, quinidine, procainamide) or Class 3 (example, amiodarone, sotalol) anti-arrhythmic drugs.
21. Is known to be currently infected or have been infected with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
22. Has received any depot preparation (sustained-release formulation) of antipsychotic drugs within 1 month (30 days) of Screening.
23. Has received clozapine for the treatment of schizophrenia (lifetime) before screening (this does not include the use of low-dose clozapine for sleep).
24. Has received monoamine oxidase (MAO) inhibitors or fluoxetine within 1 month (30 days) before Screening.
25. Is considered to be treatment resistant. Treatment resistance is defined as prior nonresponse to 2 courses of treatment with antipsychotics of different chemical classes for at least 4 weeks each at doses considered to be effective.
26. Has received electroconvulsive therapy within 6 months (180 days) before Screening.
27. Has a history of hypersensitivity to more than one distinct chemical class of drug (including anaphylaxis, rash, or urticaria caused by drugs).
28. Is considered otherwise inappropriate for the study by the investigator or Sponsor's medical monitor and/or designee.
29. Has 1 or more laboratory values outside the normal range that are considered by the investigator to be clinically significant at the Screening Visit; or has any of the following at the Screening Visit: a serum creatinine value \>1.5 times the upper limit of normal (ULN). A total serum total bilirubin value \>1.5\*ULN. A serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value \>2\*ULN, or prolactin \>= 100 nanogram/milliliter (ng/mL).
