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Two parallel-placed adjacent high-rise buildings are often linked to each other through passive control devices for vibration mitigation purposes. The mitigation efficiency of these control devices mainly depends on the characteristics of relative dynamic responses, namely, opposite-sign and same-sign responses of the two buildings. The present research first identifies an opposite-sign response factor to estimate the time ratio of opposite-sign responses. Subsequently, a structure comprising two adjacent high-rise buildings (with different natural frequency ratios) subjected to both wind and earthquake excitations is analyzed. Wind-induced responses are evaluated based on wind loads obtained from wind tunnel tests, while earthquake responses are determined through a suite of 44 natural ground-motion records. The results indicate that opposite-sign factors of the displacement, velocity, and acceleration responses under wind loads, especially at across-wind direction, are larger than those under earthquake excitations, and opposite-sign response factors under wind loads are insensitive to variation of the natural frequency ratio of the two adjacent buildings compared with those under earthquake excitations. The conclusions of this research may be helpful for wind-resistant and antiseismic design of parallel-placed adjacent high-rise buildings.