Adding far-red (FR) photons to a constant photosynthetic photon flux density (PPFD) alters photosynthesis, leaf morphology, and biomass accumulation of horticultural plants. However, the influences of partially substituting PPFD with FR photons under the same extended PPFD (ePPFD) on the growth of greenhouse lettuce (Lactuca sativa L.) is still unknown. In this study, loose-leaf lettuce (‘Dasusheng’) grown in a greenhouse in the fall was implemented using six supplementary light treatments including white plus red (WR) LEDs with substitutive FR photon flux density at 0, 10, 30, 50, 70, and 90 µmol·m−2·s−1 under the same ePPFD (WR139, WR129+FR10, WR109+FR30, WR89+FR50, WR69+FR70, and WR49+FR90, respectively). Lettuce grown with natural light only was designated as NL. The results indicated that supplementary light led to lower plant height, thicker leaves, higher biomass accumulation, higher vitamin C content, higher starch content, and higher total soluble sugar content in lettuce compared with those of lettuce grown under NL. Lettuce grown under WR139 resulted in a 40.0% decrease in plant height, 66.8% increase in leaf thickness, and 34.1% increase in shoot fresh weight compared with those of lettuce grown under NL. No significant differences were observed in leaf width, specific leaf area, shoot fresh weight, root fresh weight, shoot dry weight, root dry weight, soil plant analysis development value, apparent quantum yield, soluble protein content, and light use efficiency of lettuce among the WR139, WR129+FR10, and WR109+FR30 treatments. Furthermore, decreased trends were observed in the biomass accumulation and maximum net photosynthetic rate of lettuce with the increased substituted FR photon flux density. However, an opposite trend was found in the maximum photochemical quantum yield. In conclusion, partially substituting PPFD with FR photons at 10 to 30 μmol·m−2·s−1 had similar effects on the biomass accumulation and nutritional quality of greenhouse lettuce. The FR photons should be applied with the consideration of photon flux density because the results also demonstrated negative effects of excess substituted FR photons for PPFD.