diff --git a/doc/source/whatsnew/v0.22.0.txt b/doc/source/whatsnew/v0.22.0.txt
index c3a0e3599a0f9..5a5d6e92c21e8 100644
--- a/doc/source/whatsnew/v0.22.0.txt
+++ b/doc/source/whatsnew/v0.22.0.txt
@@ -282,7 +282,7 @@ I/O
 Plotting
 ^^^^^^^^
 
--
+- :func: `DataFrame.plot` now raises a ``ValueError`` when the ``x`` or ``y`` argument is improperly formed (:issue:`18671`)
 -
 -
 
diff --git a/pandas/plotting/_core.py b/pandas/plotting/_core.py
index adaaa206edadd..9d74a308f79c8 100644
--- a/pandas/plotting/_core.py
+++ b/pandas/plotting/_core.py
@@ -19,7 +19,7 @@
     is_number,
     is_hashable,
     is_iterator)
-from pandas.core.dtypes.generic import ABCSeries
+from pandas.core.dtypes.generic import ABCSeries, ABCDataFrame
 
 from pandas.core.common import AbstractMethodError, _try_sort, _any_not_none
 from pandas.core.generic import _shared_docs, _shared_doc_kwargs
@@ -1680,9 +1680,8 @@ def _plot(data, x=None, y=None, subplots=False,
     else:
         raise ValueError("%r is not a valid plot kind" % kind)
 
-    from pandas import DataFrame
     if kind in _dataframe_kinds:
-        if isinstance(data, DataFrame):
+        if isinstance(data, ABCDataFrame):
             plot_obj = klass(data, x=x, y=y, subplots=subplots, ax=ax,
                              kind=kind, **kwds)
         else:
@@ -1690,7 +1689,7 @@ def _plot(data, x=None, y=None, subplots=False,
                              % kind)
 
     elif kind in _series_kinds:
-        if isinstance(data, DataFrame):
+        if isinstance(data, ABCDataFrame):
             if y is None and subplots is False:
                 msg = "{0} requires either y column or 'subplots=True'"
                 raise ValueError(msg.format(kind))
@@ -1702,15 +1701,19 @@ def _plot(data, x=None, y=None, subplots=False,
                 data.index.name = y
         plot_obj = klass(data, subplots=subplots, ax=ax, kind=kind, **kwds)
     else:
-        if isinstance(data, DataFrame):
+        if isinstance(data, ABCDataFrame):
             if x is not None:
                 if is_integer(x) and not data.columns.holds_integer():
                     x = data.columns[x]
+                elif not isinstance(data[x], ABCSeries):
+                    raise ValueError("x must be a label or position")
                 data = data.set_index(x)
 
             if y is not None:
                 if is_integer(y) and not data.columns.holds_integer():
                     y = data.columns[y]
+                elif not isinstance(data[y], ABCSeries):
+                    raise ValueError("y must be a label or position")
                 label = kwds['label'] if 'label' in kwds else y
                 series = data[y].copy()  # Don't modify
                 series.name = label
diff --git a/pandas/tests/plotting/test_frame.py b/pandas/tests/plotting/test_frame.py
index 5c72d778a1220..3b3f6666340b8 100644
--- a/pandas/tests/plotting/test_frame.py
+++ b/pandas/tests/plotting/test_frame.py
@@ -2170,6 +2170,26 @@ def test_invalid_kind(self):
         with pytest.raises(ValueError):
             df.plot(kind='aasdf')
 
+    @pytest.mark.parametrize("x,y", [
+        (['B', 'C'], 'A'),
+        ('A', ['B', 'C'])
+    ])
+    def test_invalid_xy_args(self, x, y):
+        # GH 18671
+        df = DataFrame({"A": [1, 2], 'B': [3, 4], 'C': [5, 6]})
+        with pytest.raises(ValueError):
+            df.plot(x=x, y=y)
+
+    @pytest.mark.parametrize("x,y", [
+        ('A', 'B'),
+        ('B', 'A')
+    ])
+    def test_invalid_xy_args_dup_cols(self, x, y):
+        # GH 18671
+        df = DataFrame([[1, 3, 5], [2, 4, 6]], columns=list('AAB'))
+        with pytest.raises(ValueError):
+            df.plot(x=x, y=y)
+
     @pytest.mark.slow
     def test_hexbin_basic(self):
         df = self.hexbin_df