Dark Matter Search Results from 4.2  Tonne-Years of Exposure of the LUX-ZEPLIN (LZ) Experiment

We report results of a search for nuclear recoils induced by weakly interacting massive particle (WIMP) dark matter using the LUX-ZEPLIN (LZ) two-phase xenon time projection chamber. This analysis uses a total exposure of 4.2±0.1 tonne-years from 280 live days of LZ operation, of which 3.3±0.1 tonne-years and 220 live days are new. A technique to actively tag background electronic recoils from ^{214}Pb β decays is featured for the first time. Enhanced electron-ion recombination is observed in two-neutrino double electron capture decays of ^{124}Xe, representing a noteworthy new background. After removal of artificial signal-like events injected into the dataset to mitigate analyzer bias, we find no evidence for an excess over expected backgrounds. World-leading constraints are placed on spin-independent (SI) and spin-dependent WIMP-nucleon cross sections for masses ≥9  GeV/c^{2}. The strongest SI exclusion set is 2.2×10^{-48}  cm^{2} at the 90% confidence level and the best SI median sensitivity achieved is 5.1×10^{-48}  cm^{2}, both for a mass of 40  GeV/c^{2}.