We previously identified an interaction between the RNA polymerase II (Pol II) subunit RPB7 and the phosphatase CTDP1 in regulating transcription termination-reinitiation. Here, we establish that CTDP1 dephosphorylates a unique Pol II phospho-isoform modified at Tyr1, Ser5, and Ser7 of its C-terminal domain. This activity is critical for recruiting the Mediator complex and modulating transcriptional efficiency. Furthermore, by integrating phosphoproteomic and immunoprecipitation-mass spectrometry data, we reveal that CTDP1 also governs the phosphorylation of numerous RNA splicing factors. Our findings position CTDP1 as a master coordinator that integrates transcription with RNA splicing.