The purpose of the study is to evaluate the efficacy and safety of tirbanibulin 10 milligrams per gram (mg/g) ointment when applied to a treatment field (TF) larger than 25 square centimeters (cm^2) and up to 100 cm^2 in adult participants with actinic keratosis (AK).

Inclusion Criteria:

• Participants having a TF on the face or balding scalp (excluding lips, eyelids, and inside nostrils and ears) that contains >= 4 to less than or equal to (<=) 12 clinically typical, visible, and discrete (non-confluent) AK lesions and measures more than 25 cm2 (example, one cheek) and up to approximately 100 cm2 (example, mid face).
• Participants willing to avoid excessive sunlight or UV light exposure, including the use of tanning beds, to the face or scalp during the study.
• Women of childbearing potential (WOCBP), that is, fertile, defined as a female in the life period from menarche and until becoming post-menopausal (no menses for 12 months without an alternative medical cause) or permanently sterile (with hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3 months prior to screening) must have a negative urine pregnancy test using a highly sensitive method at screening and on Day 1 prior to treatment administration, be using highly effective methods of birth control for at least 30 days or 1 menstrual cycle, whichever is longer, and until at least 30 days or 1 menstrual period, whichever is longer, after the last dose of investigational product, agree to have pregnancy tests while in the study and at the end of the study, and agree not to be egg (oocyte) donors while on study and until at least 30 days or 1 menstrual period, whichever is longer, after the last dose of investigational product.
• Sexually active males with female partners who are WOCBP must agree to use two forms of contraception, one of which must be barrier contraception, from screening through 90 days after their last dose of study treatment. All non-sterile male participants must agree not to donate sperm or attempt conception from screening through 90 days following their last dose of study treatment.
• Participants should have ability to understand the purpose and risks of the trial, willingness and ability to comply with the protocol, and provided written informed consent in accordance with institutional and regulatory guidelines.

Exclusion Criteria:

• Participants with clinically atypical and/or rapidly changing AK lesions in the TF; hyperkeratotic or hypertrophic lesions, recalcitrant disease (defined as failure to respond to cryosurgery on 2 previous occasions) and/or cutaneous horn; history of invasive SCC, Bowen's disease, BCC, or other malignant tumors in the TF; any other dermatological disease that causes difficulty with examination.
• Location of the TF is on any location other than the face or balding scalp, within 5 centimeter (cm) of an incompletely healed wound, within 5 cm of a suspected BCC or other neoplasms, periorbital, lips, or nostrils.
• Participants having a previous treatment with tirbanibulin 10 mg/g ointment.
• Females who are pregnant or nursing or seeking to become pregnant.
• Participants having intention to use any concomitant medication that is not permitted by this protocol or failure to undergo the required washout period for a particular prohibited medication or therapy.
• Participants with anticipated need for inpatient hospitalization or inpatient surgery from Day 1 to Day 113.
• Participants with history of sensitivity and/or allergy to any of the ingredients in the study medication.
• Participants with significant abnormalities on the medical history, physical examination (PE) findings, vital signs, clinical chemistry, or hematology results that in the judgment of the investigator may interfere with the interpretation of the results.
• Participants with skin disease (example; atopic dermatitis, psoriasis, eczema) or condition (example; scarring, open wounds) that, in the opinion of the investigator, might interfere with the study conduct or evaluations, or which exposes the participant to unacceptable risk by study participation.
• Participants with significant uncontrolled or unstable medical diseases or conditions that, in the opinion of the investigator, would expose the participant to unacceptable risk by study participation.
• Participants who have participated in an investigational drug trial during which an investigational study medication was administered within 30 days or 5 half-lives of the investigational product, whichever is longer, before dosing in the current study.
• Participant who is employee or a relative to an employee at the research site or the Sponsor.