This paper reports the experimental results of the vortex-induced vibration (VIV) response of an inclined flexible pipe with various oblique angles (θ) ranging from 0° to 60°. The flexible pipe with an aspect ratio of 75 was fixed at both ends. The VIV response was examined in the reduced velocity range of 4.02–17.55 to evaluate the IP (independence principle) validity. The experimental results illustrate that the spatial distribution of response amplitudes and associated modal weights varies with θ, and the differences are enlarged in the mode transition cases. With increasing the θ, the onset normal reduced velocity (Urn) of mode transition shifts to a lower value and the Urn range of mode transition is narrowed gradually. Additionally, the mode competition is enhanced, resulting in pronounced traveling waves with accelerated propagation speed. The vortex shedding pattern varies along the span, presenting the 2S (two vortices are shed per cycle) and P + S (a pair of vortices and a single vortex are shed from two sides of the cylinder in one cycle) patterns at the upstream and downstream pipe segments, respectively. The streamwise distance between two adjacent vortices is enlarged with the increase in θ. The pipe placed with different inclined angles presents different partitions of coupling pattern, and the Urn range of each sub-region is different. By comprehensive consideration of the spatial–temporal evolution of VIV response, the mode transition features, the coupling pattern, and vortex shedding characteristics, the IP is invalid in predicting the VIV of flexible pipe.