Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by a progressive-fibrosing phenotype. IPF has been associated with aberrant HDAC activities confirmed by our immunohistochemistry studies on HDAC6 overexpression in IPF lung tissues. We herein developed a series of novel <i>h</i>HDAC6 inhibitors, having low inhibitory potency over <i>h</i>HDAC1 and <i>h</i>HDAC8, as potential pharmacological tools for IPF treatment. Their inhibitory potency was combined with low <i>in vitro</i> and <i>in vivo</i> toxicity. Structural analysis of <b>6h</b> and structure-activity relationship studies contributed to the optimization of the binding mode of the new molecules. The best-performing analogues were tested for their efficacy in inhibiting fibrotic sphere formation and cell viability, proving their capability in reverting the IPF phenotype. The efficacy of analogue <b>6h</b> was also determined in a validated human lung model of TGF-β1-dependent fibrogenesis. The results highlighted in this manuscript may pave the way for the identification of first-in-class molecules for the treatment of IPF.