Sustainable agriculture in the Huang–Huai–Hai Plain of China is threatened by subsoil compaction and the decline of winter wheat productivity induced by inappropriate tillage regimes. We investigated the effects of optimizing the tillage regime on grain filling and its relationship with flag leaf senescence post-anthesis in winter wheat. Four treatments were compared: rotary tillage, strip rotary tillage, strip rotary tillage with a 2-year subsoiling interval (STS), and conventional plowing tillage. STS produced higher chlorophyll content and leaf area indexes than other treatments, resulting in a greater photosynthetically active radiation capture ratio. The net photosynthesis rate of flag leaves from 14 to 28 days after anthesis and dry matter accumulation at maturity were higher in STS than in other treatments. Sucrose content and sucrose phosphate synthase activity of flag leaves first increased and then decreased during grain filling and were highest in STS. STS increased superoxide dismutase activity, increased soluble protein content, and reduced malondialdehyde concentrations in flag leaves after the middle grain-filling stages, resulting in reduced premature senescence. This consequence extended the active grain filling period and increased grain weight. The highest yields were observed in STS, reaching 10,451 kg ha–1 in 2014–2015 and 10,074 kg ha–1 in 2015–2016, owing to increased spike numbers and 1000-kel weight. Overall, our study suggested that STS could substantially increase photosynthetic capacity and delay leaf senescence, thus promoting grain filling rate and increasing winter wheat yields.