In the past few years, hybrid organic-inorganic perovskite solar cells (PSCs) have been widely investigated and the power conversion efficiency (PCE) rocket-boosted from 3.8% to 23.7%, [1] originating from the excellent properties of perovskite materials such as appropriate and adjustable bandgap, high absorption coefficient, good charge carrier mobility, long carrier diffusion length, low recombination rate, and high tolerance of chemical defects. [2] Among various compositions, hybrid organic-inorganic PSCs based on mixed-cation formamidinium/methylammonium (FA/MA) perovskites have been attractive not only due to higher efficiency, but also better thermal stability, higher phase stability and more robust long-term stability than the FA cation or MA cation only counterparts. [3] For instance, MA cation only perovskite, i.e., MAPbI 3 , has a very low tetragonal-to-cubic phase transformation temperature of about 60 °C. FA Crystal orientation has a great impact on the properties of perovskite films and the resultant device performance. Up to now, the exquisite control of crystal orientation (the preferred crystallographic planes and the crystal stacking mode with respect to the particular planes) in mixed-cation perovskites has received limited success, and the underlying mechanism that governs device performance is still not clear. Here, a thermodynamically favored crystal orientation in formamidinium/methylammonium (FA/MA) mixed-cation perovskites is finely tuned by composition engineering. Density functional theory calculations reveal that the FA/MA ratio affects the surface energy of the mixed perovskites, leading to the variation of preferential orientation consequently. The preferable growth along the (001) crystal plane, when lying parallel to the substrates, affects their charge transportation and collection properties. Under the optimized condition, the mixed-cation perovskite (FA 1-x MA x PbI 2.87 Br 0.13 (Cl)) solar cells deliver a champion power conversion efficiency over 21%, with a certified efficiency of 20.50 ± 0.50%. The present work not only provides a vital step in understanding the intrinsic properties of mixed-cation perovskites but also lays the foundation for further investigation and application in perovskite optoelectronics.