To clarify the photosynthetic physiological response of mulberry seedlings under mixed saline–alkali stress, different saline–alkali combinations were prepared to study its effect on leaf water content, chlorophyll content, and changes of chlorophyll fluorescence parameters of mulberry seedlings leaves. Different saline–alkali combinations were composed of three salt concentrations (50, 100, and 200 mmol L−1) and four pH gradients (7.0, 8.0, 9.0, and 10.0) in different proportions, of which salt concentrations were prepared with two neutral salts (NaCl and Na2SO4) and two alkaline salts (Na2CO3 and NaHCO3) in different proportions. The results showed that different pH levels had relatively limited influence on chlorophyll fluorescence parameters of mulberry seedling leaves when the salt concentration was 50 mmol L−1 and 100 mmol L−1, but the photochemical activity decreased slightly with the increase of the pH value in the 100 mmol L−1 treatment. When salt concentrations increased to 200 mmol L−1, the photochemical efficiency of PSII in mulberry seedling leaves decreased significantly. With the increase of the pH value, the reduction of the PSII reaction center activity in mulberry seedling leaves was accelerated. Mixed saline–alkali stress also resulted in a significant decline in the electron transport rate (ETR) of mulberry seedling leaves, which was mainly due to the decrease in activity of the oxygen-evolving complex (OEC) on the PSII donor side and the blockage of electron transfer from QA to QB on the PSII acceptor side. This electron transfer on the PSII acceptor side was the main target point of saline–alkali stress. At a salt concentration of 100 mmol L−1, mulberry seedlings dissipated excess light energy by increasing non-photochemical quenching (NPQ). However, at the 200 mmol L−1 salt concentration, the protective ability of NPQ decreased, and the reduction was more significant at a high pH value, which led to the accumulation of excess excitation energy (1 − qP)/NPQ and the aggravation of photoinhibition. Saline–alkali mixed stress also significantly changed the energy distribution parameters of the PSII reaction center. A higher salt concentration and pH value led to inactivation or degradation of the PSII reaction center and reduced the ability of antenna pigment to capture light energy. Under the interaction of high salt concentration and high pH value, mulberry seedlings dissipated excess excitation energy mainly in the form of heat energy with the decrease of NPQ. In conclusion, the effects of salt and pH value on the PSII function in mulberry seedlings leaves were minimal under low salt concentrations, and there was no significant interaction between them. However, salt and pH showed significant interactions under the high salt concentration, and the higher pH value affected photoinhibition in PSII under saline–alkali stress. Therefore, the influence of total alkalinity and alkalinity should be considered when planting mulberry in high salinity areas.