Autophagosomes are formed during autophagy, which is activated by hypoxia and starvation. Autophagy is important for mast cell degranulation. We hypothesized that autophagy is a key feature in the pathogenesis of systemic sclerosis (SSc). We examined SSc clinical features and mast cell density across the presence and severity of autophagy. Skin punch biopsy was performed on 33 SSc patients and 6 healthy controls (HC). Autophagy was evaluated by immunofluorescence on paraffin sections using LC3-FITC staining on these patients. The intensity of staining and mast cell density was examined across clinical features in 19 of the SSc patients. Presence of autophagosome formation was assessed by EM in 17 of the SSc patients and 4 HC. In our SSc study population, 29 of subjects were female and 23 were limited cutaneous. Twenty-nine of 33 SSc patients had autophagy by LC3-FITC staining. Intensity of staining decreased with longer duration of SSc (p = 0.09) and RP (p = 0.10). Bloating and distention differed across level of intensity staining (Wilcoxon signed-rank test, p = 0.05), with the greatest levels among those with moderate intensity. On EM, autophagosome formation was present in 16 of 17 SSc patients and no HC. All SSc patients had perivascular mast cells. Autophagy was present in 29 of 33 SSc patients, and none of our HC suggesting importance in pathogenesis. Autophagy staining was greater among those with shorter duration of SSc. Bloating and distention were higher in patients with moderate autophagy staining. Perivascular mast cells were present in all SSc patients. The role of autophagy in vasculopathy and mast cell activation in SSc warrants further studies.