Background: The deep nitrogen (N) fertilization coupled with mechanical pot-seedling transplanting rice (DNF-MPT) is an effective alternative to traditional transplanted rice with broadcasting fertilizer, however, little is known about its effects on grain yield, nutrient accumulation, and economic profitability. In present study, a two-year field experiment was conducted in early seasons (March-July) of 2019 and 2020. All seedlings were transplanted by DNF-MPT, whereas four treatments were designed as: MD: mechanized deep placement of all fertilizers as base fertilizer; MDB: mechanized deep placement of 70% fertilizers as basal fertilizer, 30% broadcasting fertilizers at panicle initiation stage; MB: manual broadcasting of 40%, 30% and 30% fertilizers at the transplanting, tillering and panicle initiation stages, respectively; and CK: no fertilizer was applied during entire growth stages. Results: The results indicated that MD treatment substantially improved the grain yield by 33.48-36.35%, total nitrogen accumulation (TNA) by 26.38-44.15%, total phosphorus accumulation (TPA) by 28.72-30.23%, and total potassium accumulation (TKA) by 25.61-37.33%, respectively, compared with MB treatment. Deep placement of N fertilization treatments i.e., MD and MDB remarkably promoted root morphological indexes and total root dry weight. Furthermore, nitrate reductase (NR), glutamine synthetase (GS) activities and total chlorophyll content (total Chl) of leaves were also enhanced under deep placement of N fertilizer. Overall, the MD treatment had the highest benefit cost ratio (BCR) owing to high gross returns and low input costs. Conclusions: Deep placement of N fertilizer coupled with mechanical pot-seedling transplanting rice could be better alternative to conventional rice production system with more economic benefits.