Background: Multiple life-prolonging therapies have been approved for mCRPC, for example novel hormonal therapies (NHT; abiraterone [abi], enzalutamide [enza]), docetaxel (doc), cabazitaxel, sipuleucel-T, and radium-223. This study describes real-world treatment patterns with life-prolonging therapies and sequencing among men with mCRPC in the US Medicare population. Methods: Men newly diagnosed with mCRPC were identified in Medicare fee-for-service claims during 1/1/2014–6/30/2019. Adult men were required to have a diagnosis of prostate cancer, metastasis diagnosis, castration-resistance using a published claims-based algorithm, and continuous insurance coverage for ≥1 year before and ≥6 months after index mCRPC diagnosis unless patients died. Treatment patterns of life-prolonging therapies after mCRPC diagnosis and sequencing were described. Results: Among 14,780 men with mCRPC, median age was 75 years, 10% used NHT in the year prior to mCRPC, and 3% had prior taxane therapy. Median follow-up after mCRPC diagnosis was 17 months. 22% of men received no life-prolonging therapy after mCRPC diagnosis, 78% received ≥1 line of therapy with life-prolonging treatment after mCRPC diagnosis, 42% had ≥2, and 20% had ≥3. The most common first-line (1L) therapies were abi (36%), enza (28%), and doc (16%). The most common second-line (2L) therapies were enza (33%), abi (28%), and doc (15%). The most common third-line (3L) therapies were doc (24%), enza (19%), and abi (17%). Median time from start of 1L to next line of therapy or end of follow-up was 13.7 months, 10.9 months from the start of 2L, and 8.9 months from the start of 3L. The most common 1L to 2L treatment sequences among men with ≥2 lines were NHT followed by a different NHT (33%), chemotherapy followed by NHT (14%), and NHT followed by chemotherapy (13%). There were 5,630 men with ≥2 lines of therapy and ≥1 NHT, of whom 53% had ≥2 NHTs. Conclusions: Substantial proportions of men with mCRPC did not receive a life-prolonging therapy or had only 1L therapy after mCRPC diagnosis, with a 50% fall-off rate after each line of therapy. NHTs were the most common 1L and 2L therapies, and NHT followed by a different NHT was the most common treatment sequence. Further research is needed to understand how treatment patterns change as NHTs and doc are used earlier in the disease continuum and new therapies are introduced and ultimately to identify optimal treatment sequencing.