This randomized, double-blind, placebo-controlled study will evaluate the safety and efficacy of lebrikizumab administered subcutaneously (SC) in adult participants with persistent moderate to severe atopic dermatitis (AD) who are inadequately controlled by topical corticosteroids (TCS). The study includes a screening visit, a 2-week run-in period, a 12-week blinded treatment period, and an 8-week safety follow-up period. Following screening visit, eligible participants will enter in run-in period (Days - 14 to - 1) during which a protocol-specified topical therapy regimen will be initiated. At the end of the run-in period, participants who have: 1) demonstrated compliance with the protocol-specified TCS regimen, and 2) who continue to fulfill the eligibility criteria will be randomized.

Inclusion Criteria:

• AD diagnosed by the Hanifin/Rajka criteria and that has been present for at least 1 year at screening
• Moderate to severe AD as graded by the Rajka/Langeland criteria at screening
• History of inadequate response to a >/= 1 month (within the 3 months prior to the screening visit) treatment regimen of at least daily TCS and regular emollient for treatment of AD
• EASI score >/= 14 at screening and end of the run-in period
• IGA score >/= 3 (5-point scale) at screening and end of the run-in period
• AD involvement of >/= 10% BSA at screening
• Pruritus VAS score >/= 3 at screening

Exclusion Criteria:

• Past and/or current use of any anti-interleukin (IL)-13 or anti-IL-4/IL-13 therapy, including lebrikizumab
• Use of an investigational agent within 4 weeks prior to screening or within 5 half-lives of the investigational agent, whichever is longer
• History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
• Use of any complementary, alternative, or homeopathic medicines including, but not limited to, phytotherapies, traditional or non-traditional herbal medications, essential fatty acids, or acupuncture within 7 days prior to the run-in period or need for such medications during the study
• Evidence of other skin conditions; including, but not limited to, T-cell lymphoma or allergic contact dermatitis
• Evidence of, or ongoing treatment (including topical antibiotics) for active skin infection at screening
• Other recent infections meeting protocol criteria
• Active tuberculosis requiring treatment within the 12 months prior to Visit 1
• Evidence of acute or chronic hepatitis or known liver cirrhosis
• Known immunodeficiency, including human immunodeficiency virus (HIV) infection
• Use of a topical calcineurin inhibitor (TCI) at the time of screening, unless the participant is willing to stop TCI use during the study (including the run-in period) and, in the investigator's opinion, it is safe to do so
• Clinically significant abnormality on screening electrocardiogram (ECG) or laboratory tests that, in the opinion of the investigator, may pose an additional risk in administering study drug or TCS to the participant
• Known current malignancy or current evaluation for a potential malignancy, including basal or squamous cell carcinoma of the skin or carcinoma in situ
• History of malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer