Mutations in tRNAs can lead to mis-incorporation of an amino acid into a growing polypeptide chain that differs from what is specified by the mRNA in a process known as mistranslation. As mistranslating tRNAs modify how the genetic message is decoded, they have potential as therapeutic tools to treat diseases caused by nonsense and missense mutations. However, they also produce proteome-wide mis-made proteins which can disrupt proteostasis. To better understand the impact of mistranslating tRNA variants, we profile the proteome and phosphoproteome of yeast expressing three different mistranslating tRNAs. The first is a proline tRNA with a G3:U70 base pair in its acceptor stem that mis-incorporates alanine at proline codons (Pro→Ala; Hoffman et al. 2017). The other two are serine tRNAs with either a UGG proline or UCU arginine anticodon which mis-incorporate serine at proline (Pro→Ser) or serine at arginine codons (Arg→Ser), respectively (Berg et al. 2017, 2019b). This submission includes 24 DDA raw files from whole proteome samples digested with LysC, 24 DDA raw files from whole proteome samples digested with LysC and trypsin and 24 DIA raw files from whole proteome samples digested with LysC and trypsin.